Advances in technology have resulted in a dramatic change in the nature of genetic investigation. Innovation in bioinformatics has made a wide variety of databases, which include nucleotide and protein sequence data, genetic map data, genetic markers, and many other resources, accessible to investigators. The refinement of high-throughput sequencing protocols has also had its effect, with the result that the relative ease of obtaining sequence data has promoted a sequence-based characterization of the genome of a nature such that information is readily transferable from laboratory to laboratory. The infrastructure that is necessary to utilize this technology-intensive investigation requires a considerable investment in computers, instrumentation, and technical support. To address this change in the nature of genetic analysis in the context of an academic medical center, we have initiated a genome analysis effort to support investigations at the Brigham and Women's Hospital. This effort is intended to provide necessary infrastructure and genetic expertise to expedite the execution of the significant number of NIH- supported research efforts that are presently in progress, and to inform the development of future studies. This center will also serve as a nucleus for introduction of additional technologies in genetic analysis as they are inevitably developed, and will provide a focus for the education of academic physicians, both at the trainee and more senior investigator levels, in the appropriate technologies of contemporary and future genetic analysis. This shared instrument grant (SIG) application requests and ABI377 automated sequencing instrument. Given the crucial role of high through- put DNA sequence analysis in gene discovery, this instrument represents the cornerstone of our planned genetics program. To implement this effort, the Brigham and Women's Hospital has committed sufficient space and resource to equip a state-of-the-art molecular biology laboratory, as well as support for both faculty-level and technical support personnel.